PROJECT SUMMARY/ABSTRACT Rheumatic Heart Disease (RHD) remains a significant public health problem in lower and middle-income countries (LMIC), accounting for over 300,000 deaths world-wide. RHD is a sequela of Acute Rheumatic Fever (ARF) caused by Group A Streptococcus (GAS). The Benzathine Penicillin Prophylaxis (BPP), through tri- weekly intramuscular injection of benzathine penicillin G, remains the mainstay of intervention to delay and prevent the sequelae among ARF and RHD patients by preventing repeat GAS infections. Two major obstacles exist to the optimal utilization of this effort. First, despite proven benefits, BPP adherence remains low. Unfortunately, there is very little knowledge on the factors associated with BPP adherence. Even in countries, like Nepal, which has a nation-wide free BPP program serving about 6000 patients, there is absence of a robust system to prospectively track and study these patients. Second, largely because RHD is initially asymptomatic, only a fraction of those who would benefit are enrolled in BPP programs. There is a dearth of information and evidence on potentially high-yield approaches like the screening of first-degree relatives of RHD patients to identify asymptomatic, early-stage RHD patients who may benefit from BPP. We will combine the resources and expertise at the University of Washington with those from our existing partners at two leading Nepali hospitals (Manmohan Cardiothoracic, Vascular and Transplant Center and Dhulikhel Hospital) to first create an easy to use, scalable, comprehensive electronic RHD registry and enroll BPP patients (n=1000) from these sites. In Aim 1, we will examine whether patient socio-demographic, clinical, and health services-related characteristics are associated with BPP adherence. We will use the BPP registry to collect important covariate information and adherence outcomes to address this aim. In Aim 2, we will determine the feasibility of screening first-degree relatives of known RHD patients. We will invite first- degree relatives (n=150) of 50 known RHD patients (enrolled in the BPP registry) for echocardiographic screening for RHD. We will assess the participation rate; time and cost required to complete the screening of each participant; and estimate the prevalence of RHD in these first degree relatives. These are vital preliminary data needed to design a study to determine the efficacy and cost-effectiveness of a screening approach that focuses on first-degree relatives. Our proposal harnesses one of the largest RHD patient pools in the world for establishing a robust RHD-related quality improvement and research platform that serves as a solid foundation for conducting larger epidemiologic, interventional, and implementation studies on RHD risk, prevention, and treatment.